The vocal folds are the primary vibratory tissues essential for voice production. In humans, there are two vocal folds, each consisting of a stratified squamous epithelium, which encapsulates the lamina propria (LP) and the vocalis muscle (Hirano, Phonosurgery: Basic and Clinical Investigations. Otologia (Fukuoka), 1975. 21: p. 239-442; Hirano, Structure of the vocal fold in normal and diseased states: anatomical and physical studies. Proceedings of the Conference on the Assessment of Vocal Pathology; The American Speech-Language-Hearing Association, 1981.11: p. 11-27; each of which is incorporated herein by reference). The lamina propria is a soft tissue that can be roughly divided into three layers: superficial, intermediate, and deep. The vocal ligament is comprised of the intermediate and deep layers of the lamina propria, and the vocal muscle is situated deep to the vocal ligament. See FIGS. 1a-1b. Vocal cord mucosa (i.e., the superficial lamina propria and the overlying epithelium) has long been recognized as the key vibratory layer critical for normal phonation (Bishop, J., Experimental Researches into the Physiology of the Human Voice. The London & Edinburgh Philosophical Magazine & Journal of Science, 1836; incorporated herein by reference). The superficial lamina propria (SLP) is a relatively acellular and pliable soft tissue and is the key constituent of the phonatory mucosa responsible for vibration. It must be identified, assessed, and preserved in most voice surgical procedures (Zeitels, S. M., Hillman, R. E., Franco, R. A., Bunting, G., Voice and Treatment Outcome from Phonosurgical Management of Early Glottic Cancer. Annals of Otology, Rhinology and Laryngology, 2002. 111 (Supplement 190): p. 1-20; Zeitels, S. M., Hillman, R. E., Desloge, R. B., Mauri, M., Doyle, P. B., Phonomicrosurgery in Singers & Performing Artists: Treatment Outcomes, Management Theories, & Future Directions. Annals of Otology, Rhinology, & Laryngology, 2002. 111 (Supplement 190): p. 21-40; Zeitels, S. M., Healy, G. B., Laryngology and Phonosurgery. New England Journal of Medicine, 2003. 349(9): p. 882-92; each of which is incorporated herein by reference). Diminished pliability of vocal cord mucosa typically results in permanent hoarseness (Zeitels, S. M., Hillman, R. E., Franco, R. A., Bunting, G., Voice and Treatment Outcome from Phonosurgical Management of Early Glottic Cancer. Annals of Otology, Rhinology and Laryngology, 2002. 111 (Supplement 190): p. 1-20; Zeitels, S. M., Hillman, R. E., Desloge, R. B., Mauri, M., Doyle, P. B., Phonomicrosurgery in Singers & Performing Artists: Treatment Outcomes, Management Theories, & Future Directions. Annals of Otology, Rhinology, & Laryngology, 2002. 111 (Supplement 190): p. 21-40; Zeitels, S. M., Healy, G. B., Laryngology and Phonosurgery. New England Journal of Medicine, 2003. 349(9): p. 882-92; each of which is incorporated herein by reference). This diminished pliability can result from benign tumors, malignant tumors, diseases, and intubation (e.g., for anesthesia or prolonged intensive care unit respiratory support). Even self-induced insult to the vocal folds in the form of excessive speaking (phonotrauma) over an extended period of time or environmental insults such as smoke, alcohol, or stomach acid from reflux disease can result in stiffening and scarring of the superficial lamina propria. One of the most common defects is the deposition of subepithelial type I collagen in the vocal cord phonatory mucosa resulting in scarring of the SLP.
There have been attempts to restore the SLP using autograft fat tissue, but such attempts have had limited success (Zeitels, S. M., Sulcus, Scar, Synechia, and Web, in Atlas of Phonomicrosurgery and Other Endolaryngeal Procedures for Benign and Malignant Disease. 2001, Singular: San Diego. p. 133-151; incorporated herein by reference). Currently, there has been no clinically feasible and reproducible method that has been demonstrated to restore SLP pliability, thereby repairing phonatory mucosal stiffness and eliminating or reducing the associated hoarseness. To date there is simply no synthetic material or autograft that will restore lost pliability to phonatory mucosa to resolve the disordered vocal cord vibration and the associated permanent hoarseness (Zeitels, S. M., Blitzer, A., Hillman, R. E., Anderson, R. R., Foresight in Layngology and Laryngeal Surgery: A 2020 Vision. Ann Otol Rhinol Laryngol, 2007. 116 (Supplement 198): p. 1-16; incorporated herein by reference). All current strategies just change the shape and position of the dysfunctional vocal fold to achieve better valvular closure (Zeitels, S. M., Jarboe, J., Franco, R. A., Phonosurgical Reconstruction of Early Glottic Cancer. Laryngoscope, 2001. 111: p. 1862-1865; Kriesel, K. J., Thibeault, S. L., Chan, R. W., Suzuki, T., VanGroll, P. J., Bless, D. M., Ford, C. N., Treatment of vocal fold scarring: Rheological and histological measures of homologous collagen matrix. Annals of Otology, Rhinology, and Laryngology, 2002. 111: p. 884-889; each of which is incorporated herein by reference). These techniques enhance voice formation by diminishing aerodynamic incompetency, a surgical maneuver that was done for the first time almost a century ago (Brunings, W., Eine neue Behandlungsmethode der Rekurrenslahmungen. Verhandl Deutsch Vereins Deutscher Laryngologen, 1911. 18:93-151; which is incorporated herein by reference). These strategies only achieve severely limited results and do not address the anatomic, physiologic, and/or biomechanical deficit.